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Pediatric and Developmental Pathology

, Volume 8, Issue 5, pp 550–556 | Cite as

Cytogenetic Findings in Pediatric T-Lymphoblastic Lymphomas: One Institution’s Experience and a Review of the Literature

  • Dale A. Ellison
  • David M. Parham
  • Jeffrey R. Sawyer
Original Article

Abstract

Cytogenetic analyses of lymphomas commonly reveal nonrandom chromosomal abnormalities, but there are relatively few reports in childhood lymphoblastic lymphoma (LL). We retrospectively reviewed G-banded karyotypic analyses performed at Arkansas Children’s Hospital between 1990 and 2004. Six children (2 to 20 years old) had LL that presented as mediastinal or cervical masses and had a T-cell immunophenotype and clonal abnormalities. The cytogenetic findings in these 6 patients were as follows: 46,XX,−7,inv(9)(p11q12),der (12)t(7;12)(q11.2;p13),t(16;18)(p13.1;q21),+22 in patient 1; 47,XX,+9,del(9)(q11q22)x2 in patient 2; 72−119, XY,+X,+1,+1, inv(2) (p11q13),−3,+5,+6,+7,+10,−12,−16, −21,−21,−22,+mar in patient 3; 48,XY,+5,+20,t(7;9) (q32;q34) in patient 4; 47∼48,XX,der(10)t(10;14)(q23; q11.2),+12, del(12)(p12)x2, −14,del(16)(q22q22),+?add (19)(p13.3) in patient 5; and 48∼49,XY,+7,+8,t(11;19) (q23;p?13.3),+der(19)t(11;19)[cp20] in patient 6. Eleven chromosome breakpoints in 6 of our patients (7q11, 12p13, 16p13, 18q21, 9q11, 2p11, 2q13, 7q32, and 7q23) have been reported in other patients with acute lymphoblastic leukemia or LL and involved regions containing TEL, ABL, E2A, MLL, and T-cell receptor-α genes. A review of the cytogenetic findings of these and other cases of LL reveals that clonal aberrations are common and most frequently involve T-cell receptor gene regions. The aberrations show some features similar to those of acute lymphoblastic leukemia and are not unique to LL, thus furnishing additional evidence of the equivalence of these two diseases. The cytogenetic features of LL may be helpful in the diagnosis of pediatric lymphomas and undifferentiated neoplasms.

Keywords

lymphoblastic lymphoma cytogenetics pediatrics 

References

  1. 1.
    Knowles DM. Lymphoblastic lymphoma. In: Knowles DM, eds. Neoplastic Hematopathology. Baltimore, MD: Williams & ilkins, 1992;715–747Google Scholar
  2. 2.
    Kaneko Y, Frizzera G, Shikano T, Kobayashi H, Maseki N, Sakurai M. Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). Leukemia 1989;3:886–892PubMedGoogle Scholar
  3. 3.
    ISCN. An International System for Human Cytogenetic Nomenclature. Basel: S. Karger, 1995Google Scholar
  4. 4.
    Ohyashiki K, Iwabuchi A, Fujieda H, Suzuki A, Nakano M, Ohyashiki JH, Toyama K, Serizawa H, Amemiya R, Hayata Y. Change in a complex translocation involving band 7q34 and 9p- in a case of T-cell lymphoblastic lymphoma. Cancer 1990;65:1533–1537PubMedGoogle Scholar
  5. 5.
    Hashimoto K, Miura I, Chyubachi A, Saito M, Miura AB. Correlations of chromosome abnormalities with histologic and immunologic characteristics in 49 patients from Akita, Japan with non-Hodgkin lymphoma. Cancer Genet Cytogenet 1995;81:56–65CrossRefPubMedGoogle Scholar
  6. 6.
    National Cancer Institute. CGAP: The Cancer Genome Anatomy Project. http://www.cgap.nci.nih.gov. 2003
  7. 7.
    Head DR, Behm FG. Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood. Semin Diagn Pathol 1995;12:325–334PubMedGoogle Scholar
  8. 8.
    Rubin CM, Le Beau MM. Cytogenetic abnormalities in childhood acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol 1991;13:201–16Google Scholar
  9. 9.
    Kaneko Y, Variakojis D, Kluskens L, Rowley JD. Lymphoblastic lymphoma: cytogenetic, pathologic, and immunologic studies. Int J Cancer 1982;30:273–279PubMedGoogle Scholar
  10. 10.
    Li D, Noyes I, Shuler C, Milo GE. Cloning and sequencing of CATR1.3, a human gene associated with tumorigenic conversion. Proc Natl Acad Sci USA 1995;92:6409–6413PubMedGoogle Scholar
  11. 11.
    Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P, Reifenberger G. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 1998;58:1798–1803PubMedGoogle Scholar
  12. 12.
    Tagge EP, Hanson P, Re GG, Othersen HB Jr, Smith CD, Garvin AJ. Paired box gene expression in Wilms’ tumor. J Pediatr Surg 1994;29:134–141CrossRefPubMedGoogle Scholar
  13. 13.
    Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the Children’s Oncology Group. J Clin Oncol 2002;20:2672–2679CrossRefPubMedGoogle Scholar
  14. 14.
    Pilozzi E, Muller-Hermelink HK, Falini B, Wolf-Peeters C, Fidler C, Gatter K, Wainscoat J. Gene rearrangements in T-cell lymphoblastic lymphoma. J Pathol 1999;188:267–270CrossRefPubMedGoogle Scholar
  15. 15.
    Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002;1:75–87.CrossRefPubMedGoogle Scholar
  16. 16.
    Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, Sallan SE, Lander ES, Golub TR, Korsmeyer SJ. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002;30:41–47CrossRefPubMedGoogle Scholar
  17. 17.
    Heerema NA, Sather HN, Sensel MG, Kraft P, Nachman JB, Steinherz PG, Lange BJ, Hutchinson RS, Reaman GH, Trigg MG, Arthur DC, Gaynon PS, Uckun FM. Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children’s Cancer Group. J Clin Oncol 1998;16:1270–1278PubMedGoogle Scholar
  18. 18.
    Bayly R, LeBrun DP. Role for homodimerization in growth deregulation by E2a fusion proteins. Mol Cell Biol 2000;10:5789–5796Google Scholar
  19. 19.
    Kletzel M, Olzewski M, Huang W, Chou PM. Utility of WT1 as a reliable tool for the detection of minimal residual disease in children with leukemia. Pediatr Dev Pathol 2002;5:269–275CrossRefPubMedGoogle Scholar
  20. 20.
    Kobayashi H, Espinosa R, III, Fernald AA, Begy C, Diaz MO, Le Beau MM, Rowley JD. Analysis of deletions of the long arm of chromosome 11 in hematologic malignancies with fluorescence in situ hybridization. Genes Chromosomes Cancer 1993;8:246–252PubMedGoogle Scholar
  21. 21.
    Mecucci C, Michaux JL, Tricot G, Louwagie A, Van den BH. Rearrangements of the short arm of chromosome No. 6 in T-cell lymphomas. Leuk Res 1985;9:1139–1148CrossRefPubMedGoogle Scholar
  22. 22.
    Rubnitz JE, Downing JR, Pui CH, et al. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol 1997;15:1150–1157PubMedGoogle Scholar
  23. 23.
    Ono Y, Fukuhara N, Yoshie O. Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T-ALL. J Biol Chem 1997;272:4576–4581.16.PubMedGoogle Scholar
  24. 24.
    Rubin CM, Le Beau MM. Cytogenetic abnormalities in childhood acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol 1991;13:202–216PubMedGoogle Scholar
  25. 25.
    Reddy KS, Perkins SL. Advances in the diagnostic approach to childhood lymphoblastic malignant neoplasms. Pathol Patterns Rev 2004;122(suppl 1):S3–S18Google Scholar
  26. 26.
    Dabaja BS, Ha CS, Thomas DA et al. The role of local radiation therapy for mediastinal disease in adults with T-cell lymphoblastic lymphoma. Cancer 2002;94:2738–2744CrossRefPubMedGoogle Scholar
  27. 27.
    Morel P, Lepage E, Brice P, et al. Prognosis and treatment of lymphoblastic lymphoma in adults: a report of 80 patients. J Clin Oncol 1992;10:1078–1085PubMedGoogle Scholar
  28. 28.
    Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del DV Jr, Medeiros LJ. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992;16:236–245PubMedCrossRefGoogle Scholar
  29. 29.
    Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ. Nonrandom chromosome abnormalities in lymphoma. Cancer Res 1983;43:2975–2984PubMedGoogle Scholar
  30. 30.
    Bohlander SK, Muschinsky V, Schrader K, Siebert R, Schlegelberger B, Harder L, Schemmel V, Fonatsch C, Ludwig WD, Hiddemann W, Dreyling MH. Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients. Leukemia 2000;14:93–99CrossRefPubMedGoogle Scholar
  31. 31.
    Chenevix-Trench G, Brown JA, Tyler GB, Behm FG. Chromosome analysis of 30 cases of non-Hodgkin’s lymphoma. Med Oncol Tumor Pharmacother 1988;5:17–32PubMedGoogle Scholar
  32. 32.
    Hecht F, Morgan R, Hecht BK, Smith SD. Common region on chromosome 14 in T-cell leukemia and lymphoma. Science 1984;226:1445–1447PubMedGoogle Scholar
  33. 33.
    Inhorn RC, Aster JC, Roach SA, Slapak CA, Soiffer R, Tantravahi R, Stone RM. A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity. Blood 1995;85:1881–1887PubMedGoogle Scholar
  34. 34.
    Konishi H, Sakurai M, Nakao H, Maseki N, Kaneko Y, Yagiri Y, Notohara K, Frizzera G. Chromosome abnormalities in malignant lymphoma in patients from Kurashiki: histological and immunophenotypic correlations. Cancer Res 1990;50:2698–2703PubMedGoogle Scholar
  35. 35.
    Levine EG, Arthur DC, Frizzera G, Peterson BA, Hurd DD, Bloomfield CD. There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin’s lymphomas. Blood 1985;66:1414–1422PubMedGoogle Scholar
  36. 36.
    Maitra A, McKenna RW, Weinberg AG, Schneider NR, Kroft SH. Precursor B-cell lymphoblastic lymphoma. A study of nine cases lacking blood and bone marrow involvement and review of the literature. Am J Clin Pathol 2001;115:868–875PubMedGoogle Scholar
  37. 37.
    Maseki N, Kaneko Y, Sakurai M, Kurihara M, Sampi K, Shimamura K, Takayama S. Chromosome abnormalities in malignant lymphoma in patients from Saitama. Cancer Res 1987;47:6767–6775PubMedGoogle Scholar
  38. 38.
    Mikraki V, Jhanwar SC, Filippa DA, Wollner N, Chaganti RSK. Distinct patterns of chromosome abnormalities characterize childhood non-Hodgkin’s lymphoma. Br J Haematol 1992;80:15–20PubMedGoogle Scholar
  39. 39.
    Nomdedeu JF, Melo M, Lopez O, Rivera J, Aventin A, Sierra J. T-cell lymphoblastic lymphoma associated with the t(6;11)(q27;q23). Haematologica 2001;86:218–219PubMedGoogle Scholar
  40. 40.
    Offit K, Parsa NZ, Jhanwar SC, Filippa D, Wachtel M, Chaganti RS. Clusters of chromosome 9 aberrations are associated with clinico-pathologic subsets of non-Hodgkin’s lymphoma. Genes Chromosomes Cancer 1993;7:1–7PubMedGoogle Scholar
  41. 41.
    Okada M, Tada M, Kanda N, Masuda M, Mizoguchi H, Kazuma M, Wada E, Kubota K, Nomura Y. C-myb gene analysis in T-cell malignancies with del(6q). Cancer Genet Cytogenet 1990;48:229–236CrossRefPubMedGoogle Scholar
  42. 42.
    Pollak C, Hagemeijer A. Abnormalities of the short arm of chromosome 9 with partial loss of material in hematological disorders. Leukemia 1987;1:541–548PubMedGoogle Scholar
  43. 43.
    Sano K, Goji J, Kosaka Y, Nakamura H, Nakamura F, Tatsumi E. Translocation (10;12)(q24;q15) in a T-cell lymphoblastic lymphoma with myeloid hyperplasia. Cancer Genet Cytogenet 1998;105:168–171CrossRefPubMedGoogle Scholar
  44. 44.
    Schouten HC, Sanger WG, Weisenburger DD, Anderson J, Armitage JO, Nebraska Lymphoma Study Group. Chromosomal abnormalities in untreated patients with non-Hodgkin’s lymphoma: associations with histology, clinical characteristics, and treatment outcome. Blood 1990;75:1841–1847PubMedGoogle Scholar
  45. 45.
    Shikano T, Arioka H, Kobayashi R, Naito H, Ishikawa Y, Nakadate H, Hatae Y, Takeda T. Acute lymphoblastic leukemia and non-Hodgkin’s lymphoma with mediastinal mass—a study of 23 children; different disorders or different stages? Leuk Lymphoma 1994;13:161–167PubMedCrossRefGoogle Scholar
  46. 46.
    Slavutsky I, Andreoli G, Gutierrez M, Narbaitz M, Lucero G, Eppinger M. Variant (8;22) translocation in lymphoblastic lymphoma. Leuk Lymphoma 1996;21:169–172PubMedCrossRefGoogle Scholar
  47. 47.
    Thandla S, Alashari M, Green DM, Aplan PD. Therapy-related T cell lymphoblastic lymphoma with t(11;19)(q23;p13) and MLL gene rearrangement. Leukemia 1999;13:2116–2118PubMedGoogle Scholar
  48. 48.
    Thangavelu M, Huang B, Lemieux M, Tom W, Richkind KE. A t(4;11)(q21;p15) in a case of T-cell lymphoma and a case of acute myelogenous leukemia. Cancer Genet Cytogenet 2002;132:109–115CrossRefPubMedGoogle Scholar
  49. 49.
    Wan TS, Ma SK, Chan GC, Ching LM, Ha SY, Chan LC. Complex cytogenetic abnormalities in T-lymphoblastic lymphoma: resolution by spectral karyotyping. Cancer Genet Cytogenet 2000;118:24–27CrossRefPubMedGoogle Scholar

Copyright information

© Society for Pediatric Pathology 2005

Authors and Affiliations

  • Dale A. Ellison
    • 1
  • David M. Parham
    • 1
  • Jeffrey R. Sawyer
    • 1
  1. 1.Department of PathologyArkansas Children’s HospitalLittle RockUSA

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